Hepatitis is an infectious disease caused by hepatitis virus which has wide epidemic range and high incidence. Viral hepatitis is a general designation of hepatitis. Hepatitis C was initially described as non A and non B-post transfusion hepatitis. In 1989, hepatitis C virus cDNA was cloned successfully from the blood of an infected chimpanzee by Choo et al., which confirms hepatitis C virus is the pathogen of hepatitis C. Hepatitis C is a virus infectious and worldwide spread disease. It can cause a wide, formidable and chronic infection and make more people die compared with AIDS. The amount of HCV infected patients is been 3 times of that of AIDS infected patients. 2%˜3% in global population, 0.7%˜3.1% in Chinese population. 80% of HCV infectors may develop into chronic hepatitis, at least 20% will progress to cirrhosis, and 15% may develop metastasis of liver cancer. It is estimated 1.7 billion people are infected by virus which can cause permanent liver injury, even death.
There is no specific for HCV at present. Nucleoside analogues, ribavirin (and nucleotide trinitro), acyclovir (acycloguanosine), ganciclovir and so on, are used clinically. As an old product of nucleoside analogues, ribavirin has strong effect on blocking the replication of hepatitis C virus. Especially, hepatitis C is combined treated by interferon and ribavirin, by which the disease is controlled. But the virus cannot be cleaned. Sustained virologic response rate of it is not satisfied. Only 50% patients respond to it completely. For patients with HCV/HIV co-infection, the percentage decrease to 30%. In addition, nucleoside analogues cost too much and make patients bounce back to bad health if they stop taking them and result in a series of harm because of their side effect. So the urgent matter is to find anti-HCV drug with high efficiency and low toxicity.
In recent years, with further study on replication steps in lifecycle of HCV virus, some promising drug targets are found, such as HCV NS3 protease. In the replication process of HCV, it is a necessary protease. The encode of this protease is serine protease and nucleoside triphosphatase/helicase. The protease needs NS4A protein to be cofactor to make activity optimize. HCV NS3/4A protease is a key enzyme in viral replication and formation of infection virus particles and a charming target of HCV inhibitor. It is effective way to search and discover HCV N3/4A protease inhibitor to discover anti-HCV drugs.